As the human genome project progresses, the detailed structural information obtained will open up many opportunities for attacking significant biological problems that were impossible to study previously. We are interested in using the techniques of single molecule PCR to study the pattern of recombination along human chromosomes, and to study the rate of specific mutations which cause human disease in the male germ line. Using information on the physical distance between DNA polymorphisms, and the method of sperm typing, the patterns of recombination potential along a large chromosomal segment will be determined and the size of the chromosomal regions which have recombination hot spot activity will be accurately defined. The effect that structural rearrangements at the human MHC have on altering the patterns of genomic recombination will also be examined. Finally, methods to detect and quantify the level of specific mutations in the male germ line will be developed.